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Recent Advances in Thrombosis and Hemostasis 2008 pp 80–106Cite as

Structural Insights into the Life History of Thrombin

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Abstract

Thrombin is the ultimate coagulation factor. Not only is it the final protease generated by the blood coagulation cascade, it has more than 12 substrates and 5 cofactors. How thrombin specificity is directed during the four stages of hemostasis is of great interest to the medical community, as insufficient thrombin activity leads to bleeding and excessive activity results in thrombosis. Over the last three decades we have learned a great deal about how thrombin is generated and how it recognizes its several cofactors, substrates, and inhibitors. Although much has been inferred from biochemical studies, our current understanding is primarily based on numerous crystallographic structures of thrombin complexes. In this chapter I provide an overview of the multiple roles thrombin plays in the initiation, amplification, propagation, and attenuation phases of hemostasis, and describe how the special structural features of thrombin are exploited to achieve regulation and substrate selectivity.

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Authors and Affiliations

  1. Division of Structural Medicine, Thrombosis Research Unit, Cambridge Institute for Medical Research, Department of Haematology, University of Cambridge, Wellcome Trust/MRC Building, Hills Road, Cambridge, CB2 2XY, UK

    James A. Huntington

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Editors and Affiliations

  1. Department of Pathology, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Kenzo Tanaka M.D., Ph.D. (Professor Emeritus) (Professor Emeritus)

  2. Department of Biochemistry, University of Washington, J317 Health Science Center, Box 357350, Seattle, WA, 98195, USA

    Earl W. Davie Ph.D. (Professor) (Professor)

  3. School of Medicine, Internal Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Yasuo Ikeda M.D., Ph.D. (Professor) (Professor)

  4. Department of Biology, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka, 812-8581, Japan

    Sadaaki Iwanaga Ph.D. (Professor Emeritus) (Professor Emeritus)

  5. Department of Medicine, Nagoya University, 26 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

    Hidehiko Saito M.D., Ph.D. (Professor Emeritus) (Professor Emeritus)

  6. Pathophysiological and Experimental Division, Department of Pathology, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Katsuo Sueishi M.D., Ph.D. (Professor) (Professor)

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Huntington, J.A. (2008). Structural Insights into the Life History of Thrombin. In: Tanaka, K., Davie, E.W., Ikeda, Y., Iwanaga, S., Saito, H., Sueishi, K. (eds) Recent Advances in Thrombosis and Hemostasis 2008. Springer, Tokyo. https://doi.org/10.1007/978-4-431-78847-8_5

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